The present invention relates to the use of N-Acylphosphatidylethanolamine as anti-oxidant for unsaturated fatty acids.
Unsaturated fatty acids are broadly used compounds. They can be found in free form or chemically bound, as in triglycerides, phospholipids and sphingolipids. They are found broadly in nature and are important constituents of the food. Bound to glycerol, as triglycerides, they are present in plant seeds as energy store and are isolated from them as important basic compound for human and animal nutrition. In the phospholipids the unsaturated fatty acids are connected with all cellular membranes. In free form they are the initial products for the biological synthesis of important active products in living species, like e.g. prostaglandins. In all types of incidence the chemically unchanged form is the prerequisite for the accomplishment of the function assigned to the unsaturated fatty acids.
The most serious change is the oxygenation of the double bond in the fatty acid, with as a consequence peroxide formation and a radical chain reaction, which leads to a cleavage of the fatty acids. These reactions nay be in full control, but can also be uncontrolled. Examples of controlled oxidation are the metabolism of nutrition as energy source, the immunological resistance against bacteria and parasites and the synthesis of mediators like prostaglandins.
The radicals which are formed at the uncontrolled radical chain reaction can not only react with fatty acids but also with proteins and nucleic acids. The reaction products lead to pathological changes in the organism.
The uncontrolled oxidation is inhibited by anti-oxidants, which are taken up with the food, or are synthesised in the organism. Deficient nutrition, pathological changes and the process of ageing can lead to a deficiency in anti-oxidants.
The oxidation of consumption fats is always unwanted and leads to products, which are toxicologically unsat and which make the nutrient unpalatable by changes in the taste. These changes can be inhibited by anti-oxidants and as much as possible by the exclusion of oxygen.
Due to the large presence in different biological systems and the great importance of unsaturated fatty acids, the properties of anti-oxidants for the protection of unsaturated fatty acids are subject to various conditions. Up to now none of the known anti-oxidants fulfils the majority of these conditions.
The most used natural anti-oxidants are .alpha.-tocopherol and .beta.-carotene are on the one hand perfectly efficacious but unstable in the presence of oxygen and light. Also the heat stability which is important in the use of some foodstuffs like oils, is limited.
Furthermore there is a complicated isolation process or a synthesis which makes the product expensive.
Ascorbic acid has the disadvantage, that it is not soluble in oils and for that matter only effective in aqueous surroundings, so that it can inhibit the oxidation of fatty acids which are present in the fat phase only to a limited extent. A further disadvantage is the fact, that ascorbic acid can be an oxidative agent in combination with iron salts.
Furthermore synthetic phosphatides as well as phosphatides isolated from plant and animal fats and oils were investigated on their anti-oxidant properties against the autoxidation of fats and oils alone and in combination with additives.
The results obtained are however strongly contradictory.
For instance is the investigation of crude lecithin and its ethanol-soluble and ethanol-insoluble fractions described by A. Nasner in Fette, Seife, Anstrichmittel 12 (1985) pp. 477-481 to determine their anti-oxidative efficacy in storage tests with sunflower oil and lard. He found, that the anti-oxidative effects depend on the type of lecithin fraction used. The ethanol-soluble fraction of the soybean lecithin with the largest portion of phosphatidylethanolamine showed the best effects. The inhibition of the oxidation of lard with a content of a-tocopherol of less than 10 ppm is markedly greater than of sunflower oil which contains 500 ppm .alpha.-tocopherol.
According to Nasner a synergy between .alpha.-tocopherol and the phosphatides can be excluded, whilst phosphatides alone provide an anti-oxidative effect.
Comparable results are obtained by D. H. Hildebrand in JAOCS 61 (1984) pp. 552 ff. in an investigation to the anti-oxidative effects of phosphatidylcholine, phosphatidylinositol and phosphatidylethanolamine. He showed, that the oil stability increases upon addition of phosphatides alone and in combination with a-tocopherol.
A synergy between the phosphatides and .alpha.-tocopherol is assumed. The best effect shows phosphatidylethanolamine, which is also confirmed by I. S. Bhatia et al. in J. Sci. Fd. Agric. 79 (1978) pp. 77 ff.
Other investigations are in contrast with these investigations. J. H. Lee et al describe for instance in the Bulletin of the Japanese Society of Scientific Fisheries 47 (1981) pp. 881-883 the anti-oxidative effects of lipids of the Antarctic shrimp. In these investigations .alpha.-tocopherol was identified as the active substance, whereas only a synergistic effect was attributed to the phosphatides in respect to the improvement of the effects of .alpha.-tocopherol.
J. H. Lee et al in J. Biol. Chem. 47 (1983) pp. 2001 ff. investigated the anti-oxidative properties of phosphatide fractions from shrimp, egg yolk and soybeans and observed, that these fractions do not provide an anti-oxidative effect, but activate the decomposition of the peroxides formed by oxidation.
M. Kashima et al. in JAOCS 68 (1991 ) pp. 119 ff. also deny the anti-oxidative effect of phosphatides as phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine. The anti-oxidative effects of these phosphatides were determined in tocopherol-free perila oil and the same oil with an increased content in tocopherol. It was observed, that the oxidative stability of the tocopherol-free perila oil was not improved by the addition of the phosphatides, whereas on the other hand the oxidation of the perila oil with the increased content in tocopherol was strongly suppressed by the addition of phosphatidylethanolamine and phosphatidylserine. This confirms earlier results, that phosphatides alone do not provide an anti-oxidative effect, but only increase the anti-oxidative effect of .alpha.-tocopherol due to a synergistic mechanism.
Other natural anti-oxidants are plant extracts. like for instance extracts from rosemary. The disadvantages of such products are the natural variations of their composition. They often contain dyes, have an unwanted taste and smell and are difficult to obtain.
Anti-oxidants not obtained from natural sources, like BHA, BHT, TBHQ and propyl gallate all contain a sterically hindered phenyl moiety and are, as all phenols in biological systems, reactive. Investigations in recent years have shown, that BHA may cause cancer at certain concentrations in different animal species. For that reason BHA-containing foodstuffs must be marked with the text "BHA may lead to cancer, unless certain concentrations are kept" in some countries. Also the increasing awareness of environmental problems in the population has led to a steady decline in the acceptance of unnatural products in foodstuffs.